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R Valdez

Publications and source records attributed to R Valdez.

At least 19 recordsLinked to original sources

Signaling lymphocytic activation molecule expression and regulation in human intracellular infection correlate with Th1 cytokine patterns.

Induction of Th1 cytokines, those associated with cell-mediated immunity, is critical for host defense against infection by intracellular pathogens, including mycobacteria. Signaling lymphocytic activation molecule (SLAM, CD150) is a transmembrane protein expressed on lymphocytes that promotes T cell proliferation and IFN-gamma production. The expression and role of SLAM in human infectious disease were investigated using leprosy as a model. We found that SLAM mRNA and protein were more strongly expressed in skin lesions of tuberculoid patients, those with measurable CMI to the pathogen, Mycobacterium leprae, compared with lepromatous patients, who have weak CMI against M. leprae. Peripheral blood T cells from tuberculoid patients showed a striking increase in the level of SLAM expression after stimulation with M. leprae, whereas the expression of SLAM on T cells from lepromatous patients show little change by M. leprae stimulation. Engagement of SLAM by an agonistic mAb up-regulated IFN-gamma production from tuberculoid patients and slightly increased the levels of IFN-gamma in lepromatous patients. In addition, IFN-gamma augmented SLAM expression on M. leprae-stimulated peripheral blood T cells from leprosy patients. Signaling through SLAM after IFN-gamma treatment of Ag-stimulated cells enhanced IFN-gamma production in lepromatous patients to the levels of tuberculoid patients. Our data suggest that the local release of IFN-gamma by M. leprae-activated T cells in tuberculoid leprosy lesions leads to up-regulation of SLAM expression. Ligation of SLAM augments IFN-gamma production in the local microenvironment, creating a positive feedback loop. Failure of T cells from lepromatous leprosy patients to produce IFN-gamma in response to M. leprae contributes to reduced expression of SLAM. Therefore, the activation of SLAM may promote the cell-mediated immune response to intracellular bacterial pathogens.

Antibodies↗

Fingerprint ridge-count difference between adjacent fingertips (dR45) predicts upper-body tissue distribution: evidence for early gestational programming.

Fingerprint ridge counts, which remain constant from the 19th week of pregnancy, are related to fingertip growth during early gestation. Each finger corresponds neurologically to a spinal-cord segment ranging from C6 (thumb, relatively cephalad) to C8 (fifth finger, relatively caudad). The authors hypothesized that large ridge-count differences between fingertips (cephalad > caudad) might reflect fetal inhibition of caudal growth. Among 69 male Atlanta, Georgia, military recruits (1994-1997; aged 17-22 years), they tested associations of the anthropometric waist-to-thigh ratio with 20 ridge-count differences. Waist-to-thigh ratio was associated with the ridge-count difference between the right fourth and fifth fingertips only (dR45; r = 0.36, p = 0.003). The race-adjusted standardized regression coefficient was 0.22 (95% confidence interval: 0.03, 0.41). Since upper-body tissue distribution indicates disease risk, the authors then tested the association of age (an indicator of survivorship) with dR45 in a sample of 135 male patients from Bangalore, India (1989-1990; aged 38-82 years). Age was inversely associated with dR45 (r = -0.17, p = 0.04), notably among the 75 men with diabetes (r = -0.22, p = 0.06). An increased dR45 predicts an upper-body tissue distribution originating before the midpoint of pregnancy. The cause of this developmental pattern is unknown, but it may lead to reduced survivorship.

Adolescent↗

The first example of a paraben-dependent antibody to an Rh protein.

BACKGROUND: Parabens are added to a commercial LISS (C-LISS) to retard microbial growth. Paraben-dependent anti-Jk(a) has been detected by the use of C-LISS. CASE REPORT: Serum from a D+ woman reacted in antiglobulin tests with RBCs stored (2-4 hours, 22-25 degrees C) in C-LISS (Löw and Messeter formulation, Immucor). Freshly prepared C-LISS-suspended RBCs did not react; nor did RBCs stored in LISS-additive reagents, PEG, saline, or homemade LISS. RESULTS: Studies using C-LISS-stored RBCs revealed an antibody that reacted with D+ and rrV+ RBCs, but not with r'r, r"r, or rrV-VS- RBCs. All partial D RBC phenotypes tested reacted, as did D+LW-, rGr, r"Gr, r(y)r, r'(s)rV+VS+, and r'(s)rV-VS+ RBCs. The active ingredient in C-LISS was propylparaben. Other LISS ingredients were not required; saline solutions of propylparaben, ethylparaben, methyl salicylate, 2-phenoxyethanol, and butylparaben were active. Methylparaben and methyl-m-hydroxybenzoate were inactive. Reactivity to C-LISS-stored RBCs could not be inhibited by propylparaben. Reactivity with D+V- and D-V+VS+ RBCs was not separable by adsorption-elution. CONCLUSIONS: This antibody likely detects a neoantigen formed between active compounds and RBC membranes. Review of the structure of active compounds suggests that proximity between methyl and hydroxyl groups is important for binding with RBC membranes. The role of RhD is unclear; no single portion of RhD protein appears to be implicated.

Adult↗

Impaired fasting glucose, diabetes mellitus, and cardiovascular disease risk factors are associated with prolonged QTc duration. Results from the Third National Health and Nutrition Examination Survey.

BACKGROUND: Impaired glucose tolerance and diabetes mellitus have been associated with a prolonged QT interval among select populations. However, these associations remain unclear among the general population. METHODS: We examined these relationships using data from 5833 adults aged 40-90 years from NHANES III (1988-1994). Univariate differences in cardiovascular disease (CVD) risk factors were examined across tertiles of heart rate corrected QT (QTc). The association between glucose intolerance, CVD risk factors and a prolonged QTc (> or = 0.440 s) was also assessed with logistic regression adjusting for age, race, gender, education, and heart rate. RESULTS: Prolonged QTc was observed among 22.0% of persons with normal glucose tolerance (NGT), 29.9% of those with impaired fasting glucose (IFG), and among 42.2% of persons with diabetes. Hypertension, serum cholesterol, obesity, heart rate, and fasting C-peptide and serum insulin levels were associated with prolonged QTc (all: P < or = 0.05). After multivariate adjustment, persons with IFG were 1.2 times (95% CI=0.7-2.0) as likely and persons with diabetes 1.6 times (95% CI=1.1-2.3) as likely to have a prolonged QTc as persons with NGT. In addition, persons with diabetes and two or more additional CVD risk factors were 2.3 times (95% CI=1.3-4.0) as likely to have a prolonged QTc as persons with NGT and no CVD risk factors after multivariate adjustment. CONCLUSION: Diabetes was associated with an increased likelihood of prolonged QTc independent of age, race, gender, education, and heart rate. In addition, persons with diabetes and multiple CVD risk factors were more likely to have a prolonged QTc than those with NGT and no additional risk factors, suggesting that these persons may be at increased risk for cardiac arrhythmia and sudden death.

Blood Glucose↗

Waldenström macroglobulinemia caused by extranodal marginal zone B-cell lymphoma: a report of six cases.

Waldenström macroglobulinemia (WM) and its associated hyperviscosity syndrome (HVS) are generally caused by lymphoplasmacytoid lymphoma or other small B-cell lymphoproliferative disorders. WM associated with extranodal marginal zone B-cell-mucosa-associated lymphoid tissue lymphoma (EMZL/MALT-type) has not been emphasized. We describe 4 men and 2 women (age, 40-79 years) with clinical and laboratory manifestations of WM and EMZL/MALT-type involving one or more sites: lung, pericardium/pleura, ocular adnexa, nasopharynx, minor salivary gland, glossopharyngeal fold, skin, and stomach. The following immunophenotypic patterns were observed: CD20+, 6; CD43+, 3; kappa light chain restriction, 5; and lambda light chain restriction, 1. All were negative for CD5, CD10, and cyclin D1 expression. A clonal paraproteinemia was present in each (IgM kappa, 4; IgM lambda, 1; biclonal IgM kappa/IgA kappa, 1). All 4 patients tested had elevated plasma viscosity; clinical HVS occurred in 3, and 2 required emergency plasmapheresis. These findings suggest that EMZL/MALT-type can cause WM and that the laboratory evaluation of EMZL/MALT-type should include serum protein electrophoresis/immunofixation, and plasma viscosity measurements and urine immunofixation in select cases. EMZL/MALT-type should be considered in the differential diagnosis in patients with clinicopathologic features of WM.

Adult↗

Relation of birth weight to lean and fat thigh tissue in young men.

BACKGROUND: Birth weight is positively associated with body mass index (BMI, kg/m2) in later life, but is inversely associated with cardiovascular risk. To understand this paradox, we examined the relationships between birth weight, adult BMI, and estimations of lean and fat tissue in young men. METHODS: From 192 applicants for military service (ages 17-22 y, mean BMI 23.2 kg/m2) with known birth weights we measured the circumference and anterior skinfold thickness at midthigh to estimate thigh muscle+bone area and subcutaneous fat area. Linear regression models including birth weight as the independent variable were adjusted for race and adult height. RESULTS: BMI was linearly associated with birth weight (standardized regression coefficient, [SRC]=+0.27; P=0.0004), as was the thigh muscle+bone area (SRC=+0.22; P=0.0029), but not the thigh subcutaneous fat area (SRC=+0.13; P=0.086). The BMI-birth weight association was reduced by 68% when the regression model was further adjusted for thigh muscle+bone area. Separate adjustment for thigh subcutaneous fat, however, reduced the BMI-birth weight association by only 30%. Waist circumference was also associated with birth weight (SRC=+0.24; P=0.0014), sagittal abdominal diameter was weakly associated (SRC=+0.17; P=0.028), but waist/thigh ratio and abdominal diameter index were not associated with birth weight. INTERPRETATION: The larger BMI associated with higher birth weight may reflect increments in lean tissue more than increments in fat. Birth weight's influence on lean tissue is observed in the thigh and, among fit young men, perhaps at the waist. Increased muscularity in young men may partly explain the cardiovascular benefit in middle age ascribed to higher birth weight.

Abdomen↗

Type 2 diabetes among North American children and adolescents: an epidemiologic review and a public health perspective.

OBJECTIVES: To review the magnitude, characteristics, and public health importance of type 2 diabetes in North American youth. RESULTS: Among 15- to 19-year-old North American Indians, prevalence of type 2 diabetes per 1000 was 50.9 for Pima Indians, 4.5 for all US American Indians, and 2.3 for Canadian Cree and Ojibway Indians in Manitoba. From 1967-1976 to 1987-1996, prevalence increased 6-fold for Pima Indian adolescents. Among African Americans and whites aged 10 to 19 years in Ohio, type 2 diabetes accounted for 33% of all cases of diabetes. Youth with type 2 diabetes were generally 10 to 19 years old, were obese and had a family history of type 2 diabetes, had acanthosis nigricans, belonged to minority populations, and were more likely to be girls than boys. At follow-up, glucose control was often poor, and diabetic complications could occur early. CONCLUSIONS: Type 2 diabetes is an important problem among American Indian and First Nation youth. Other populations have not been well studied, but cases are now occurring in all population groups, especially in ethnic minorities. Type 2 diabetes among youth is an emerging public health problem, for which there is a great potential to improve primary and secondary prevention.

Adolescent↗

Diffuse duodenitis associated with ulcerative colitis.

Backwash ileitis and postcolectomy pouchitis are well-recognized complications of ulcerative colitis (UC), whereas inflammation of the proximal small intestine is not. In contrast, small intestinal disease at any level is common in Crohn's disease (CD). Despite this well-established and accepted dogma, rare cases of histologically proven diffuse duodenitis (DD) associated with UC appear in the literature. In this study, we report our experience with similar cases exhibiting this unusual inflammatory phenomenon. Routine histologic sections from four cases of DD associated with well-documented UC were reviewed and the findings correlated with all available medical records. Multiple endoscopic biopsies showing histologic features of UC and colectomy specimens confirming severe ulcerative pancolitis were available for all cases. Varying degrees of active chronic inflammation and architectural mucosal distortion identical to UC were observed in pre- and postcolectomy duodenal biopsies of one of four and four of four cases, respectively. Similar inflammatory patterns were present postoperatively in the ileum in three of four cases and in the jejunum in one case. Endorectal pull-through (ERPT) procedures were performed in three of four patients and an end-to-end ileorectal anastomosis was done in one patient. Despite extensive upper gastrointestinal tract involvement, none of the patients developed postsurgical Crohn's-like complications during a follow-up period of 12 to 54 months. This suggests that patients with pancolitis and DD do not necessarily have CD, but rather may have UC and, most importantly, that successful ERPT procedures may be performed in these patients.

Adolescent↗

Possible relationship between altered fatty acid composition of serum, platelets, and aorta and hypertension induced by sugar feeding in rats.

To establish a relationship between alterations in fatty acid metabolism, induced by sugar ingestion, and hypertension, we analyzed fatty acid composition of serum, platelets and aorta in rats which had 30% of sugar in their drinking water for 18-20 weeks, and became hypertensive, hypertriglyceridemic and hyperinsulinemic. The fatty acid composition in sugar-fed as compared with that from control rats was as follows: in serum phospholipids, triglycerides and cholesterol ester fractions, palmitic, palmitoleic, oleic and cis-11-eicosadecaenoic acids were present in a higher proportion. In serum phospholipid fraction linoleic and arachidonic acids were decreased and a significant increase was observed in the proportion of dihomo-gamma-linolenic acid. In the membrane phospholipids of platelets and aorta, higher proportions of palmitoleic and of oleic acids were observed. Differences in fatty acid composition of phospholipids between sugar-fed and control rats are consistent with altered membrane fluidity. Altered membrane function is a potential mechanism involved hypertension in rats in sugar-induced.

Animals↗

Epidemiology.

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Adolescent↗

Impact of diabetes mellitus on mortality associated with pneumonia and influenza among non-Hispanic black and white US adults.

OBJECTIVES: This study assessed the impact of diabetes on mortality associated with pneumonia and influenza among non-Hispanic Black and White US adults. METHODS: Data were derived from the National Mortality Followback Survey (1986) and the National Health Interview Survey (1987-1989). RESULTS: Regardless of race, sex, and socioeconomic status, people with diabetes who died at 25 to 64 years of age were more likely to have pneumonia and influenza recorded on the death certificate than people without diabetes who died at comparable ages (odds ratio [OR] = 4.0, 95% confidence interval [CI] = 2.3, 7.7). For those 65 years and older, the risk remained elevated among Whites with diabetes (OR = 2.2, 95% CI = 1.7, 2.7) but not among Blacks with diabetes (OR = 1.0, 95% CI = 0.6, 1.7). It was estimated that about 17,000 (10.3%) of the 167,000 deaths associated with pneumonia and influenza that occurred in 1986 were attributable to diabetes. CONCLUSIONS: The impact of diabetes on deaths associated with pneumonia and influenza is substantial. Targeted immunizations among people with diabetes may reduce unnecessary deaths associated with pneumonia and influenza.

Adult↗

Interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) are necessary in the early stages of induction of CD4 and CD8 cytotoxic T cells by Mycobacterium leprae heat shock protein (hsp) 65 kD.

Cytotoxic T cells (CTL) may play an important role in host defence against mycobacterial infections. CD4 CTL are preferentially induced by mycobacteria, but both CD4 and CD8 CTL may be necessary components of a protective immune response. The 65-kD mycobacterium heat shock protein (hsp65) is a poor inducer of CTL in multibacillary leprosy (MB) patients. In this study we evaluate the possible role of cytokines in modulating the cytotoxic activity of CTL from leprosy patients and normal individuals (N) against autologous macrophages presenting Mycobacterium leprae hsp65. Our results show that hsp65-specific CTL were generated from both CD4 and CD8 lymphocytes. In N, individual cytokines as well as the combination of them were able to modify the hsp65-induced cytotoxic activity. The effect of cytokines on leprosy patients' lymphocytes was different in MB and paucibacillary (PB) patients. Thus, IL-6, IL-2, IFN-gamma or TNF-alpha did not modify the generation of hsp65-CTL from either MB (with or without an erythema nodosum episode (ENL)) or PB. In all the patients the simultaneous addition of two cytokines was required in order to increase CTL generation. In MB, IL-6 plus IFN-gamma or IL-2 increased both CD4 and CD8 CTL, while TNF-alpha plus IFN-gamma up-regulated only CD4 CTL. In PB, CD8 CTL were prominent with IL-6 plus IFN-gamma, while the increase was significant in CD4 CTL with IL-6 plus IL-2. Down-regulation of CTL was observed by addition of IL-4, IL-10, anti-IFN-gamma or anti-TNF-alpha in N controls. Our data demonstrate that IFN-gamma and TNF-alpha must be present for at least the first 60 h of the induction stage in order to generate full hsp65 CTL. Hence, IFN-gamma and TNF-alpha would be key factors in the generation of hsp65 CTL.

Adolescent↗

Longitudinal changes in cardiovascular risk from childhood to young adulthood in offspring of parents with coronary artery disease: the Bogalusa Heart Study.

CONTEXT: Although the association between parental coronary artery disease (CAD) and its risk factors in the offspring is known, the timing and the course of development of risk factors from childhood to adulthood in the offspring is not known. OBJECTIVE: To examine the association between parental CAD and longitudinal changes in risk factor profile from childhood to young adulthood in offspring. DESIGN: Cohort study. SETTING: Bogalusa, La, a semirural, biracial community. PARTICIPANTS: Individuals with clinically verified parental history of CAD (n=271) vs those without such a history (n = 1253) Mean age at first CAD event was 50 years for fathers and 52 years for mothers. MAIN OUTCOME MEASURES: Body mass index, subscapular skinfolds, blood pressure, and triglyceride, cholesterol (total, very low-density lipoprotein [VLDL-C], low-density lipoprotein [LDL-C], and high-density lipoprotein [HDL-C] cholesterols), glucose, and insulin levels. RESULTS: The offspring of parents with CAD were consistently overweight beginning in childhood. Their levels of total serum cholesterol, LDL-C, plasma glucose, and insulin became significantly higher at older ages, because of a higher rate of increase in these risk factors over time. In adulthood, the offspring with a positive parental history had a higher prevalence of obesity (body mass index >85th percentile in the National Health and Nutrition Examination Survey I, 35% vs 26%, P=.01), elevated total cholesterol (>6.2 mmol/L [240 mg/dL], 8.4% vs 4.8%, P=.05) and LDL-C levels (>4.1 mmol/L [160 mg/dL], 12.4% vs 4.7%, P=.05), and hyperglycemia (glucose, >6.6 mmol/L, 2.7% vs 0.4%, P<.001), as well as a higher coexistence of these conditions (P=.01). Further, the prevalence of dyslipidemia, either involving only LDL-C or LDL-C in combination with HDL-C or triglycerides or both, was significantly higher in the adult offspring with parental CAD. CONCLUSIONS: Offspring of parents with early CAD were overweight beginning in childhood and developed an adverse cardiovascular risk factor profile at an increased rate. These observations have important implications for prevention and intervention.

Adolescent↗